Transmission

The most efficient transmission of HCV is associated with large or repeated percutaneous exposures, such as transfused blood and transplanted organs from infected donors, and drug-use equipment shared between injection drug users. Sexual and household exposure to infected individuals, perinatal exposure, and percutaneous exposures in the health care setting have also been associated with transmission of HCV in the United States.

In other countries, percutaneous transmission of HCV has occurred through contaminated instruments, equipment, and supplies used in procedures of traditional medicine, folk medicine, tattooing, body piercing, and commercial barbering. Transmission by these sources has not been documented in the United States.

Transfusions and Transplants

Before 1986, the risk of acquiring HCV infection from transfusion was 5% or more per transfused unit. As a result of changes in the donor population and the use of serologic screening tests, transfusion-associated HCV infection has declined dramatically, and today is estimated at 0.01% to 0.001% per transfused unit. It can be assumed that the use of anti-HCV negative organ and tissue donors has had a similar effect on HCV transmission from transplantation. Persons infected earlier by transfusion make up approximately 7% of all persons with chronic HCV infections.

For hemophilia patients, viral inactivation of clotting factor concentrates and use of recombinant products has virtually eliminated these products as sources of HCV infection. In 1994, however, the first outbreak of hepatitis C associated with contaminated intravenous (IV) immunoglobulin was reported in the United States. A single product, Gammagard (Baxter Healthcare Corporation, Deerfield, Illinois), was associated with this outbreak. Infection was associated with lots of Gammagard produced from plasma screened by second version anti-HCV assays that were positive for HCV RNA. Intramuscular (IM) immune globulin has never been associated with the transmission of any infectious disease in the United States. Currently, all immune globulin products (IV and IM) sold in the United States must have undergone an inactivation procedure or be found HCV RNA negative before release.

Injection and Other Illegal Drug Use

Since 1989, the number of cases of acute hepatitis C among injection drug users has declined dramatically. Both the incidence and prevalence of HCV infection, however, remain high in this group, and half of all recent and remote HCV infections are associated withillegal drug use. Injection drug users quickly acquire HCV infection after they start to inject drugs. One study reported that from 50% to 80% of users were anti-HCV positive within 12 months of initiating drug injection. Even persons who may have only experimented a few times many years ago are at risk of being infected with HCV.

HCV infection has also been associated with a history of intranasal cocaine use. It is not known whether this type of noninjection illegal drug use is an independent mode of transmission -- perhaps by sharing blood contaminated straws -- or is an indication that both injection and noninjection illegal drug use is practiced.

Nosocomial Transmission

Although annual incidence rates of almost 2% have been reported for hemodialysis patients, these patients are underrepresented among cases of acute disease. This discrepancy is due both to underreporting and to high rates of subclinical infection. The prevalence of anti-HCV positivity among hemodialysis patients is 10% to 20%. Both incidence and prevalence studies have found an association between anti-HCV positivity and increasing years on dialysis that was independent of blood transfusion. These studies, as well as investigations of dialysis-associated outbreaks of hepatitis C, suggest that HCV may be transmitted between patients in a dialysis center because of poor infection control practices, particularly the sharing of medication vials and supplies between patients.

Nosocomial transmission of HCV is possible in other health care settings if breaks in technique occur or if disinfection procedures are inadequate and contaminated equipment is shared between patients. Such transmission has not been documented in the United States. A published report from Spain described HCV transmission from a cardiac surgeon to five patients, but did not identify the factors responsible for transmission.

Occupational Exposure to Blood

The average incidence of anti-HCV seroconversion among health care workers after unintentional needle sticks or sharps exposures is 1.8% (range, 0%-7%). One study from Japan reported an HCV infection incidence of 10% based on detection of HCV RNA by PCR. Seroprevalence studies have reported average anti-HCV rates of 1% among hospital-based health care workers, and in one study, a history of accidental needle sticks was independently associated with anti-HCV positivity. Although no follow-up studies have documented transmission associated with mucous membrane or nonintact skin exposures, the transmission of HCV from a blood splash to the conjunctiva was described in one case report.

Sexual and Household Contact

HCV may be transmitted by sexual and household exposure to an infected contact and exposure to multiple sex partners, but the efficiency of transmission from these exposures appears to be low. Among male and female heterosexual and male homosexual patients attending clinics for sexually transmitted diseases who had no history of injection drug use, the prevalence of anti-HCV has been found to average 5% (range, 1% to 18%). Factors associated with anti-HCV positivity include greater numbers of sex partners, a history of other sexually transmitted diseases, and failure to use a condom.

Among eight seroprevalence studies of long-term spouses of patients with chronic hepatitis C who had no other risk factors, the average anti-HCV prevalence was 5%. Five of these studies, however, found none of the spouses to be anti-HCV positive, and three studies found that the prevalence of anti-HCV ranged from 2% to 15%. Among nine seroprevalence studies of non-sexual household contacts of patients with chronic hepatitis C, the average anti-HCV prevalence was 4%. Two of these studies found none of the household contacts to be anti-HCV positive, and seven studies found that the prevalence of anti-HCV ranged from 1% to 11%. The presumed mechanism of transmission was inapparent percutaneous or permucosal exposure to infectious blood or body fluids containing blood. Although the infected contacts reported no other commonly recognized risk factors for hepatitis C, most of these studies were done in countries where it has been suggested that transmission of HCV infection may be associated with exposures commonly experienced in the past from contaminated equipment used in traditional and nontraditional medical procedures. In a recent investigation in the United States by the Centers for Disease Control and Prevention (CDC), an HCV-infected mother transmitted HCV to her hemophilic child while performing intravenous home therapy, presumably by accidentally sticking herself with a needle and then using the contaminated needle in the child.

The risk of HCV transmission through sexual activity and household contact is controversial; however, the available data indicate that transmission from these exposures does appear to occur -- although with a very low frequency. During the period 1991 through 1995, 15% of patients reported with acute hepatitis C had a history of sexual exposures without percutaneous risk factors as the source of their infection. Two-thirds of these patients had a sexual partner who was found to be anti-HCV positive. An anti-HCV positive household contact was the only source found for 3% of the cases reported with hepatitis C.

Perinatal Exposure

Among infants born to women who were positive for anti-HCV and negative for anti-HIV, evidence of HCV infection has been found in an average of 5% (range, 0% to 25%) based on detection of anti-HCV, and in a similar proportion (6%) based on detection of HCV RNA. The average transmission rate for infants born to women co-infected with HCV and HIV was higher; 14% (range, 5% to 36%) based on detection of anti-HCV, and 17% based on detection of HCV RNA. Biochemical hepatitis developed in all of these HCV-infected infants. Two studies of infants born to anti-HCV positive, anti-HIV negative women have suggested that the risk of perinatal transmission is related to the titer of HCV RNA. Other studies, however, indicate that there may be factors other than viral titer that influence transmission. Approximately two-thirds of infants infected through perinatal transmission have persistently elevated ALT levels. These infants do not appear to be symptomatic; however, more studies that include long-term follow-up are needed to fully understand what the ultimate outcome for these infants will be.

The transmission of HCV infection through breast milk has not been documented. In the five studies that have evaluated infants born to HCV-infected women, the average rate of infection was 4% in both breast-fed and bottle-fed infants.

Changes in Risk Factors for Transmission

The relative importance of the two most common exposures associated with the transmission of HCV has changed over time. Blood transfusion, which accounted for a substantial proportion of HCV infections acquired more than 10 years ago, accounts for only a small proportion of recently acquired infections. In 1995, the risk of transfusion-transmitted HCV infection was so low that the CDC's sentinel surveillance system was unable to detect any transfusion-associated cases of hepatitis C. In contrast, illegal (primarily injection) drug use has accounted for a substantial proportion of HCV infections during both the remote and recent past. Injection drug use currently accounts for 60% of HCV transmission in the United States. Transmission through sexual exposures has been poorly ascertained, especially among patients with chronic hepatitis C, but recent data suggest that sexual activity may account for 10% to 20% of HCV transmission among persons with acute and chronic HCV infection. Other known exposures (occupational, perinatal, etc.) each contribute a small proportion, and together account for about 10% of HCV infections. Thus, approximately 90% of HCV infections can be attributed to specific exposures. An additional 9% appear to be associated with low socioeconomic level, which may be a surrogate for specific high-risk exposures. Only 1% of patients have no distinguishing characteristics and are classified as having an unknown source for their infection.